12th Conference on Retroviruses and Opportunistic Infections Boston, Massachusetts - February 22-25, 2005

Conf Retrovir Opportunistic Infect 2005 Feb 22-25;12:abstract no. 16LB

Magnus Gisslén¹, L Rosengren¹, L Hagberg¹, and R Price^2
1Göteborg Univ, Sahlgrenska Univ Hospital, Göteborg, Sweden and ²San Francisco Gen Hosp, Univ of California, USA

BACKGROUND: Neurofilament protein (NFL) is a major structural component of myelinated axons and when measured by ELISA in the cerebrospinal fluid (CSF) can serve as a sensitive marker of axonal damage in a number of conditions.

METHODS: To assess whether antiviral treatment interruption might have an effect on the central nervous system (CNS), we measured neurofilament protein levels in 8 HIV-infected subjects stopping therapy. Decisions to stop treatment were made by the subjects and their primary caregivers independent of this study, and the subjects volunteered to undergo repeated lumbar punctures in a temporally well-defined study setting that affords an opportunity to observe the dynamics of HIV infection and resultant CSF perturbations. The subjects all had CSF HIV RNA concentrations < 50 copies/mL and were neurologically normal or identified as manifesting at the most AIDS dementia complex stage 0.5 (equivocal/subclinical) disease. Lumbar punctures were performed before treatment interruption and 1 to 6 (mean 2.9) times during the period off treatment.

RESULTS: Treatment interruption resulted in an increase in CSF neurofilament protein in 3 of the subjects, rising from < 125 to a measured maximum of 880 (at day 148), 1010 (day 58) and 10,930 ng/L (day 101) respectively in those patients (normal < 250 ng/L). All 8 subjects exhibited an increase in CSF and plasma viral load after stopping therapy, accompanied by an intrathecal immunoactivation with CSF lymphocytic pleocytosis (7 of 8 patients) and increased CSF neopterin concentration (5of 6 patients). None of the subjects experienced new neurological symptoms or signs during the periods off treatment, and of 5 tested, none showed deterioration in their QNPZ-4 score, a quantitative index of neurological performance.

CONCLUSIONS: These findings suggest that in the setting of treatment interruption, the increase in viremia may result in nervous system injury, albeit asymptomatic, within the time frame of the study. Neurofilament protein is a sensitive marker of axonal injury which in the present setting seems to disclose subclinical injury. Further studies are warranted to examine this issue further.

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Copyright © 2005 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.